Pub Date : 2025-12-01Epub Date: 2025-06-30DOI: 10.1007/s12639-025-01826-y
Emmanuel Okoro Enyi, Joy Chimuanya Nnanna
Malaria is a major public health concern responsible for significant mortality and morbidity, especially in sub-Saharan Africa. Accurate diagnosis is crucial for effective malaria control and elimination strategies. Recent studies have confirmed the existence of Plasmodium falciparum histidine-rich protein 2 and 3 (Pfhrp2/3) deficient malaria parasites, which pose significant challenges to malaria diagnosis and control. This review provides a comprehensive overview of the existing literature on Pfhrp2/3 deletions and their implications on malaria diagnosis and control. A literature search was conducted using a combination of keywords (Pfhrp2/3 deletions, malaria diagnosis, malaria control, rapid diagnostic tests) and medical subject headings (MeSH) terms (Malaria/diagnosis, Malaria/parasitology, Plasmodium falciparum/genetics) in ScienceDirect, Springer, Google Scholar, and PubMed. Studies published in English between 2018 and 2024 were included, and a total of 83 studies were selected for inclusion in the review based on predefined inclusion and exclusion criteria. This review highlights the significant challenges posed by Pfhrp2/3 deletions to malaria diagnosis and control and identifies potential solutions, including alternative diagnostic approaches and novel RDTs targeting multiple antigens.
{"title":"Overcoming the challenges of <i>Plasmodium falciparum</i> histidine-rich protein 2 and 3 deletions in malaria diagnosis and control.","authors":"Emmanuel Okoro Enyi, Joy Chimuanya Nnanna","doi":"10.1007/s12639-025-01826-y","DOIUrl":"https://doi.org/10.1007/s12639-025-01826-y","url":null,"abstract":"<p><p>Malaria is a major public health concern responsible for significant mortality and morbidity, especially in sub-Saharan Africa. Accurate diagnosis is crucial for effective malaria control and elimination strategies. Recent studies have confirmed the existence of <i>Plasmodium falciparum</i> histidine-rich protein 2 and 3 (<i>Pfhrp2/3</i>) deficient malaria parasites, which pose significant challenges to malaria diagnosis and control. This review provides a comprehensive overview of the existing literature on <i>Pfhrp2/3</i> deletions and their implications on malaria diagnosis and control. A literature search was conducted using a combination of keywords (<i>Pfhrp2/3</i> deletions, malaria diagnosis, malaria control, rapid diagnostic tests) and medical subject headings (MeSH) terms (Malaria/diagnosis, Malaria/parasitology, <i>Plasmodium falciparum</i>/genetics) in ScienceDirect, Springer, Google Scholar, and PubMed. Studies published in English between 2018 and 2024 were included, and a total of 83 studies were selected for inclusion in the review based on predefined inclusion and exclusion criteria. This review highlights the significant challenges posed by <i>Pfhrp2/3</i> deletions to malaria diagnosis and control and identifies potential solutions, including alternative diagnostic approaches and novel RDTs targeting multiple antigens.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"834-840"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-05-17DOI: 10.1007/s12639-025-01817-z
Zeinab R Hassan, Yasmeen M Shaaban, Eman M Mahmoud, Amany Mesbah Mohammed Ali, Fatma Al-Zahraa Nabil Al-Shahed, Doaa E A Salama, Amira Nasr Ismail Elsokary, Ranya M Abdelgalil, Marwa A Alanany, Mona T Koullah, Nora Seliem, Doaa Refaat Amin, Shimaa A Mohamed, Mai Ali Mohammad Etewa, Sara Nagdy Mahmoud Mousa, Mona M Amin, Maryam Mohammed Mohammed Hamouda, Shimaa Attia Atta, Reham Abdelmonem Gadallah, Sami Mohamed Nasr
Toxoplasmosis is a common protozoal disease that can cause serious complications. Hence the available drug therapies possess limited activity against chronic forms of the disease; thus, it is urgent to find more effective agents. The current study highlighted the therapeutic activity of bone marrow mesenchymal stem cells (BMSCs) and ginger combined with spiramycin against chronic experimental toxoplasmosis. A total of 48 male Swiss albino mice were distributed into 8 groups: non-infected non-treated, infected non-treated, infected treated by spiramycin, infected treated by BMSCs, infected treated by ginger, infected treated by combined BMSCs and spiramycin, infected treated by combined BMSCs and ginger, and infected treated by combined BMSCs, ginger, and spiramycin. The evaluation was performed through parasitological counting of brain cyst burden, histopathological examination, immunohistochemical cyclooxygenase-2 (COX-2) staining assessment, serum IL-10 measurement, and apoptotic gene markers assay. The results revealed that combined BMSCs, ginger, and spiramycin displayed significantly reduced parasitic cyst burden, restored histopathological changes, decreased COX2 expression, and downregulated caspases gene expression. It can be concluded that adding BMSCs and ginger to spiramycin provides a potent therapeutic agent against chronic toxoplasmosis.
{"title":"Therapeutic outcome of bone marrow stem cells and ginger in chronic murine toxoplasmosis.","authors":"Zeinab R Hassan, Yasmeen M Shaaban, Eman M Mahmoud, Amany Mesbah Mohammed Ali, Fatma Al-Zahraa Nabil Al-Shahed, Doaa E A Salama, Amira Nasr Ismail Elsokary, Ranya M Abdelgalil, Marwa A Alanany, Mona T Koullah, Nora Seliem, Doaa Refaat Amin, Shimaa A Mohamed, Mai Ali Mohammad Etewa, Sara Nagdy Mahmoud Mousa, Mona M Amin, Maryam Mohammed Mohammed Hamouda, Shimaa Attia Atta, Reham Abdelmonem Gadallah, Sami Mohamed Nasr","doi":"10.1007/s12639-025-01817-z","DOIUrl":"https://doi.org/10.1007/s12639-025-01817-z","url":null,"abstract":"<p><p>Toxoplasmosis is a common protozoal disease that can cause serious complications. Hence the available drug therapies possess limited activity against chronic forms of the disease; thus, it is urgent to find more effective agents. The current study highlighted the therapeutic activity of bone marrow mesenchymal stem cells (BMSCs) and ginger combined with spiramycin against chronic experimental toxoplasmosis. A total of 48 male <i>Swiss albino</i> mice were distributed into 8 groups: non-infected non-treated, infected non-treated, infected treated by spiramycin, infected treated by BMSCs, infected treated by ginger, infected treated by combined BMSCs and spiramycin, infected treated by combined BMSCs and ginger, and infected treated by combined BMSCs, ginger, and spiramycin. The evaluation was performed through parasitological counting of brain cyst burden, histopathological examination, immunohistochemical cyclooxygenase-2 (COX-2) staining assessment, serum IL-10 measurement, and apoptotic gene markers assay. The results revealed that combined BMSCs, ginger, and spiramycin displayed significantly reduced parasitic cyst burden, restored histopathological changes, decreased COX2 expression, and downregulated caspases gene expression. It can be concluded that adding BMSCs and ginger to spiramycin provides a potent therapeutic agent against chronic toxoplasmosis.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1012-1021"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-30DOI: 10.1007/s12639-025-01849-5
Patrick O Sakyi, Samuel K Kwofie, Theresa Manful Gwira, Christine Moore, Cynthia Amisigo, Emmanuel Broni, Whelton A Miller, Michael D Wilson, Richard K Amewu
The current therapeutic agents for the treatments of visceral leishmaniasis are ineffective, and cytotoxic. Therefore, there is the urgent need for new chemotypes for the treatment of the disease with novel mechanisms of action. In our previous investigation, we identified the triazolopyridazine, STOCK6S-84928 as a potential inhibitor of Leishmania donovani sterol methyltransferase (LdSMT) with IC50 value of 118.3 µM. To improve the biological activity of the initial hit compound, we hereby describe the results of structural-activity relationship studies on STOCK6S-84928 via chemical modifications on the scaffold and virtually screening of 250 compounds obtained against the Modeller generated LdSMT structure. A total of 21 compounds were found to have binding energies ranging from - 7.0 to - 9.2 kcal/mol lower or comparable to the 22,26-azasterol (- 7.6 kcal/mol), the known inhibitor of the target. Molecular docking and molecular dynamics simulations revealed Ile272 and Tyr275 to be pivotal for ligand binding. The compounds were predicted to possess leishmanicidal activities with good drug-like properties. Significantly, the compounds 8, 9, 21, and 23 were predicted to possess antineoplastic, anti-inflammatory, analgesics, protein and MAP kinase inhibitory activities with probability of activity (Pa) > 0.2 and probability of inactivity (Pi) < 0.16. Through the applications of cyclization, amination, Williamson's ether synthesis, and Suzuki cross-coupling reactions, the selected analogues of STOCK6S-84928 were synthesised in moderate to high yields and characterized by FTIR, LC-MS, and NMR spectroscopy methods. In vitro antileishmanial evaluation of the synthesized compounds identified 23 as the most potent, exhibiting L. donovani promastigotes inhibitory activities with IC50 value of (1.9 ± 0.1) µM. The ortho-difluoropheneyl group as well as the triazolopyridine moieties were suspected to be responsible for the observed activity. Similarly, the compounds 10 and 16 required (0.8 ± 0.1) µM and (0.6 ± 0.0) µM, respectively to eliminate 50% of Trypanosoma brucei.
Graphical abstract:
Supplementary information: The online version contains supplementary material available at 10.1007/s12639-025-01849-5.
{"title":"Molecular docking, design, synthesis and in vitro analysis identify [1,2,4]triazolo[4,3-b]pyridazine derivatives as inhibitors of <i>Leishmania donovani</i> sterol methyltransferase.","authors":"Patrick O Sakyi, Samuel K Kwofie, Theresa Manful Gwira, Christine Moore, Cynthia Amisigo, Emmanuel Broni, Whelton A Miller, Michael D Wilson, Richard K Amewu","doi":"10.1007/s12639-025-01849-5","DOIUrl":"https://doi.org/10.1007/s12639-025-01849-5","url":null,"abstract":"<p><p>The current therapeutic agents for the treatments of visceral leishmaniasis are ineffective, and cytotoxic. Therefore, there is the urgent need for new chemotypes for the treatment of the disease with novel mechanisms of action. In our previous investigation, we identified the triazolopyridazine, STOCK6S-84928 as a potential inhibitor of <i>Leishmania donovani</i> sterol methyltransferase (<i>Ld</i>SMT) with IC<sub>50</sub> value of 118.3 µM. To improve the biological activity of the initial hit compound, we hereby describe the results of structural-activity relationship studies on STOCK6S-84928 via chemical modifications on the scaffold and virtually screening of 250 compounds obtained against the Modeller generated <i>Ld</i>SMT structure. A total of 21 compounds were found to have binding energies ranging from - 7.0 to - 9.2 kcal/mol lower or comparable to the 22,26-azasterol (- 7.6 kcal/mol), the known inhibitor of the target. Molecular docking and molecular dynamics simulations revealed Ile272 and Tyr275 to be pivotal for ligand binding. The compounds were predicted to possess leishmanicidal activities with good drug-like properties. Significantly, the compounds <b>8</b>, <b>9</b>, <b>21</b>, and <b>23</b> were predicted to possess antineoplastic, anti-inflammatory, analgesics, protein and MAP kinase inhibitory activities with probability of activity (Pa) > 0.2 and probability of inactivity (Pi) < 0.16. Through the applications of cyclization, amination, Williamson's ether synthesis, and Suzuki cross-coupling reactions, the selected analogues of STOCK6S-84928 were synthesised in moderate to high yields and characterized by FTIR, LC-MS, and NMR spectroscopy methods. In vitro antileishmanial evaluation of the synthesized compounds identified <b>23</b> as the most potent, exhibiting <i>L. donovani</i> promastigotes inhibitory activities with IC<sub>50</sub> value of (1.9 ± 0.1) µM. The <i>ortho</i>-difluoropheneyl group as well as the triazolopyridine moieties were suspected to be responsible for the observed activity. Similarly, the compounds <b>10</b> and <b>16</b> required (0.8 ± 0.1) µM and (0.6 ± 0.0) µM, respectively to eliminate 50% of <i>Trypanosoma brucei.</i></p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12639-025-01849-5.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"987-1011"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-24DOI: 10.1007/s12639-025-01874-4
M I Okpala, C F Obi, G E Aneru, O O Uzondu, C N Iheagwam, C T Oyiga, I O Ezeh, R C Ezeokonkwo, D N Onah
African animal trypanosomosis is a major constraint to livestock production in sub-Saharan Africa. Chemotherapy remains the primary control strategy, but the efficacy of various trypanocide brands in circulation in Africa, especially in Nigeria, remains uncertain. This study aimed to evaluate and compare the efficacy of selected, commonly used commercial brands of diminazene aceturate and isometamidium chloride against experimental Trypanosoma brucei brucei infection in mice. A total of 35 adult male mice were randomly assigned to seven groups of five mice each. Group 1 served as the uninfected control, while groups 2-7 were intraperitoneally (i.p.) infected with 10⁶ trypanosomes. Group 2 was left untreated, while groups 3-5 were treated with diminazene aceturate brands (TrypanocideDA 1-3) respectively at a dose of 7.0 mg/kg on day 13 post-infection (p.i). Groups 6 and 7 received isometamidium chloride brands (TrypanocideISM 1 and 2) respectively at a dose of 0.5 mg/kg on day 13 p.i. Efficacy was assessed through clinical signs, parasitaemia, haematological parameters (PCV, Hb concentration, erythrocyte count, leucocyte counts), parasite clearance time, body weight, rectal temperature, and survival. Parasite clearance was fastest in group 3 (2.4 days post-treatment) compared to other treated groups (3 days post-treatment). Diminazene aceturate-treated groups exhibited shorter relapse times than isometamidium chloride-treated groups. Treatment reversed the reduction in haematological indices across all groups. The study concluded that isometamidium chloride brands demonstrated superior efficacy compared to diminazene aceturate brands in treating T. brucei brucei infections.
{"title":"Comparative efficacy of trypanocide brands against experimental <i>Trypanosoma brucei brucei</i> infections in mice.","authors":"M I Okpala, C F Obi, G E Aneru, O O Uzondu, C N Iheagwam, C T Oyiga, I O Ezeh, R C Ezeokonkwo, D N Onah","doi":"10.1007/s12639-025-01874-4","DOIUrl":"https://doi.org/10.1007/s12639-025-01874-4","url":null,"abstract":"<p><p>African animal trypanosomosis is a major constraint to livestock production in sub-Saharan Africa. Chemotherapy remains the primary control strategy, but the efficacy of various trypanocide brands in circulation in Africa, especially in Nigeria, remains uncertain. This study aimed to evaluate and compare the efficacy of selected, commonly used commercial brands of diminazene aceturate and isometamidium chloride against experimental <i>Trypanosoma brucei brucei</i> infection in mice. A total of 35 adult male mice were randomly assigned to seven groups of five mice each. Group 1 served as the uninfected control, while groups 2-7 were intraperitoneally (i.p.) infected with 10⁶ trypanosomes. Group 2 was left untreated, while groups 3-5 were treated with diminazene aceturate brands (TrypanocideDA 1-3) respectively at a dose of 7.0 mg/kg on day 13 post-infection (p.i). Groups 6 and 7 received isometamidium chloride brands (TrypanocideISM 1 and 2) respectively at a dose of 0.5 mg/kg on day 13 p.i. Efficacy was assessed through clinical signs, parasitaemia, haematological parameters (PCV, Hb concentration, erythrocyte count, leucocyte counts), parasite clearance time, body weight, rectal temperature, and survival. Parasite clearance was fastest in group 3 (2.4 days post-treatment) compared to other treated groups (3 days post-treatment). Diminazene aceturate-treated groups exhibited shorter relapse times than isometamidium chloride-treated groups. Treatment reversed the reduction in haematological indices across all groups. The study concluded that isometamidium chloride brands demonstrated superior efficacy compared to diminazene aceturate brands in treating <i>T. brucei brucei</i> infections.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1086-1099"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145504795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-19DOI: 10.1007/s12639-025-01846-8
Eman S El-Wakil, Mohamed Farid, Walaa A El Kholy
There are few treatment options available to treat toxoplasmosis. So, investigating possible antiparasitic agents from plants and nanoparticles that are widely available and reasonably priced might be a good substitute. This study aimed to examine the effect of Portulaca oleracea (P. oleracea) aqueous and methanolic extracts as a sole agent or loaded on iron oxide nanoparticles (FeONPs) compared to spiramycin on a murine model of Toxoplasma gondii (T. gondii) ME49 strain. Forty-eight Swiss albino mice were put into eight groups: GI: uninfected negative control; GII: infected, untreated positive control; GIII, GIV, GV, GVI, GVII, and GVIII: infected, treated with spiramycin (200 mg/kg), FeONPs (2.5 mg/kg), P. oleracea aqueous extract (2.5 mg/kg), P. oleracea methanolic extractt (2.5 mg/kg), P. oleracea aqueous extract loaded on FeONPs (2.5 mg/kg) and P. oleracea methanolic extract loaded on FeONPs (2.5 mg/kg) respectively. To evaluate the treatment effectiveness, parasitological counting for T. gondii cysts and histopathological assessment for brain sections using H&E were used. Also, the immunohistochemical expression of the ionized calcium-binding adapter molecule 1 (Iba-1) was investigated. T. gondii cysts number in the infected treated mice brains was significantly reduced, with GVIII having the best therapeutic efficacy with an efficiency percentage of 84% (P > 0.000). Also, this group had a remarkable improvement in the pathological changes induced by T. gondii and the highest reduction of Iba-1 expression (P > 0.000). According to this study, P. oleracea loaded on FeONPs could be a potential therapeutic candidate for treating toxoplasmosis, and administering the medications as nanoparticles enhances their therapeutic effect.
{"title":"Promising therapeutic effects of <i>Portulaca Oleracea</i> loaded iron oxide nanoparticles in <i>Toxoplasma gondii</i> infection in mice.","authors":"Eman S El-Wakil, Mohamed Farid, Walaa A El Kholy","doi":"10.1007/s12639-025-01846-8","DOIUrl":"https://doi.org/10.1007/s12639-025-01846-8","url":null,"abstract":"<p><p>There are few treatment options available to treat toxoplasmosis. So, investigating possible antiparasitic agents from plants and nanoparticles that are widely available and reasonably priced might be a good substitute. This study aimed to examine the effect of <i>Portulaca oleracea</i> (<i>P. oleracea</i>) aqueous and methanolic extracts as a sole agent or loaded on iron oxide nanoparticles (FeONPs) compared to spiramycin on a murine model of <i>Toxoplasma gondii</i> (<i>T. gondii</i>) ME49 strain. Forty-eight Swiss albino mice were put into eight groups: GI: uninfected negative control; GII: infected, untreated positive control; GIII, GIV, GV, GVI, GVII, and GVIII: infected, treated with spiramycin (200 mg/kg), FeONPs (2.5 mg/kg), <i>P. oleracea</i> aqueous extract (2.5 mg/kg), <i>P</i>. <i>oleracea</i> methanolic extractt (2.5 mg/kg), <i>P. oleracea</i> aqueous extract loaded on FeONPs (2.5 mg/kg) and <i>P. oleracea</i> methanolic extract loaded on FeONPs (2.5 mg/kg) respectively. To evaluate the treatment effectiveness, parasitological counting for <i>T. gondii</i> cysts and histopathological assessment for brain sections using H&E were used. Also, the immunohistochemical expression of the ionized calcium-binding adapter molecule 1 (Iba-1) was investigated. <i>T. gondii</i> cysts number in the infected treated mice brains was significantly reduced, with GVIII having the best therapeutic efficacy with an efficiency percentage of 84% (<i>P</i> > 0.000). Also, this group had a remarkable improvement in the pathological changes induced by <i>T. gondii</i> and the highest reduction of Iba-1 expression (<i>P</i> > 0.000). According to this study, <i>P. oleracea</i> loaded on FeONPs could be a potential therapeutic candidate for treating toxoplasmosis, and administering the medications as nanoparticles enhances their therapeutic effect.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1022-1031"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-13DOI: 10.1007/s12639-025-01862-8
Zeinab R Hassan, Kareman M Zekry, Samar El-Sayed, Samah Gouda Ahmed, Azza Kamal Taha, Nihal A Mahmoud, Mai Ali Mohammad Etewa, Sara Nagdy Mahmoud Mousa, Rasha Elsayed Mohamed, Ayat M S Eraque, Shimaa A Mohamed, Mona Moustafa Amin Salman, Maryam Mohammed Mohammed Hamouda, Amina Mohamed Amin Tolba, Sami Mohamed Nasr, Shimaa Attia Atta, Reham Abdelmonem Mohamed, Nermeen Talaat Fahmy, Hanan A Beshlawy, Mohamed S Badr
Toxoplasmosis is a global parasitic disease that can affect the central nervous system, causing severe complications. Introducing new agents that are safe during pregnancy and more effective for chronic toxoplasmosis is essential. This study investigated the effects of combined treatments with resveratrol, nitazoxanide, and spiramycin in chronic toxoplasmosis. Fifty-four Swiss albino mice were distributed into nine groups: Group 1, non-infected control; Group 2, infected non-treated control; Group 3, infected resveratrol-treated; Group 4, infected nitazoxanide-treated; Group 5, infected spiramycin-treated; Group 6, infected resveratrol and nitazoxanide-treated; Group 7, infected resveratrol and spiramycin-treated; Group 8, infected resveratrol, nitazoxanide, and spiramycin-treated; and Group 9, infected half-dose resveratrol, nitazoxanide, and spiramycin-treated. Effectiveness was evaluated by counting brain tissue cysts, histopathological examination of liver and brain tissues, immunohistochemical analysis of brain CD8+ T expression, biochemical measurement of serum IFN-γ and tissue MDA levels, and molecular assays for iNOS and BAX gene expression. The data demonstrated that adding resveratrol to spiramycin significantly reduced brain tissue cyst load, improved underlying tissue pathology, reduced brain CD8+ T expression, and lowered serum IFN-γ, tissue MDA, iNOS, and BAX gene levels in the liver, with elevated MDA, iNOS, and BAX gene levels in the brain. These results were enhanced by adding nitazoxanide to the resveratrol and spiramycin combination. It can be concoluded that co-administration of resveratrol and nitazoxanide can synergistically enhance the therapeutic effect of spiramycin in chronic toxoplasmosis.
{"title":"The efficacy of resveratrol and nitazoxanide combination therapy in a murine model of chronic toxoplasmosis.","authors":"Zeinab R Hassan, Kareman M Zekry, Samar El-Sayed, Samah Gouda Ahmed, Azza Kamal Taha, Nihal A Mahmoud, Mai Ali Mohammad Etewa, Sara Nagdy Mahmoud Mousa, Rasha Elsayed Mohamed, Ayat M S Eraque, Shimaa A Mohamed, Mona Moustafa Amin Salman, Maryam Mohammed Mohammed Hamouda, Amina Mohamed Amin Tolba, Sami Mohamed Nasr, Shimaa Attia Atta, Reham Abdelmonem Mohamed, Nermeen Talaat Fahmy, Hanan A Beshlawy, Mohamed S Badr","doi":"10.1007/s12639-025-01862-8","DOIUrl":"https://doi.org/10.1007/s12639-025-01862-8","url":null,"abstract":"<p><p>Toxoplasmosis is a global parasitic disease that can affect the central nervous system, causing severe complications. Introducing new agents that are safe during pregnancy and more effective for chronic toxoplasmosis is essential. This study investigated the effects of combined treatments with resveratrol, nitazoxanide, and spiramycin in chronic toxoplasmosis. Fifty-four Swiss albino mice were distributed into nine groups: Group 1, non-infected control; Group 2, infected non-treated control; Group 3, infected resveratrol-treated; Group 4, infected nitazoxanide-treated; Group 5, infected spiramycin-treated; Group 6, infected resveratrol and nitazoxanide-treated; Group 7, infected resveratrol and spiramycin-treated; Group 8, infected resveratrol, nitazoxanide, and spiramycin-treated; and Group 9, infected half-dose resveratrol, nitazoxanide, and spiramycin-treated. Effectiveness was evaluated by counting brain tissue cysts, histopathological examination of liver and brain tissues, immunohistochemical analysis of brain CD8<sup>+</sup> T expression, biochemical measurement of serum IFN-γ and tissue MDA levels, and molecular assays for <i>iNOS</i> and <i>BAX</i> gene expression. The data demonstrated that adding resveratrol to spiramycin significantly reduced brain tissue cyst load, improved underlying tissue pathology, reduced brain CD8<sup>+</sup> T expression, and lowered serum IFN-γ, tissue MDA, <i>iNOS</i>, and <i>BAX</i> gene levels in the liver, with elevated MDA, <i>iNOS</i>, and <i>BAX</i> gene levels in the brain. These results were enhanced by adding nitazoxanide to the resveratrol and spiramycin combination. It can be concoluded that co-administration of resveratrol and nitazoxanide can synergistically enhance the therapeutic effect of spiramycin in chronic toxoplasmosis.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1032-1044"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-07-17DOI: 10.1007/s12639-025-01816-0
Zeinab Ahmed, Eman M Kandeel, Entsar E Badr, Tarek Aboushousha, Ayman M El-Ashkar, M Sadek, Hagar F Abdelmaksoud
Cryptosporidiosis in humans is a major contributor to diarrheal epidemics that are spread through water and have a significant impact on a global scale. Nitazoxanide (NTZ) is still the only FDA-approved drug against cryptosporidiosis, but unfortunately, it has poor water solubility and bioavailability that greatly affect its efficacy. This study aimed to test the efficacy of NTZ when used in combination with cationic and amphoteric surfactants on murine cryptosporidiosis. Fifty-four white albino female mice were separated into nine groups, with each group containing six mice that had compromised immune systems. GI: normal non-infected non-treated (healthy control). GII: infected, non-treated (infected control); GIII-GXI: infected with Cryptosporidium species oocyst and treated with: GIII: NTZ (NTZ), GIV: cationic surfactant [3-(dodecyl(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)amino)-N,N,N-triethyl-2-hydroxypropan-1-aminium chloride (GDCS)]; GV: amphoteric surfactant [sodium 3-(dodecyl(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)amino)-2-hydroxypropane-1-sulfonate (GDAS)]; GVI: NTZ and GDCS; GVII: NTZ and GDAS; GVIII: NTZ and GDCS in a critical micelle concentration (CMC); GIX: NTZ and GDAS in CMC. Parasitological, and histopathological, examinations were done. Parasitological examination revealed a statistically significant difference (P < 0.001) between the different test and control groups. GIX showed the best results, with the highest percentage of reduction of oocysts in the stool (98.21%) which was statistically significant from other test and control groups. Histopathological examination revealed marked improvement in small intestinal villi, liver, and lung tissues when NTZ was used in combination with GDCS, and GDAS, especially with GDAS CMC. Therefore, surfactant could be an excellent adjuvant therapy when combined with NTZ in the treatment of cryptosporidiosis, especially GDAS CMC.
{"title":"In vivo efficiency evaluation of nitazoxanide with cationic and amphoteric surfactants on murine cryptosporidiosis: parasitological, and histopathological studies.","authors":"Zeinab Ahmed, Eman M Kandeel, Entsar E Badr, Tarek Aboushousha, Ayman M El-Ashkar, M Sadek, Hagar F Abdelmaksoud","doi":"10.1007/s12639-025-01816-0","DOIUrl":"https://doi.org/10.1007/s12639-025-01816-0","url":null,"abstract":"<p><p>Cryptosporidiosis in humans is a major contributor to diarrheal epidemics that are spread through water and have a significant impact on a global scale. Nitazoxanide (NTZ) is still the only FDA-approved drug against cryptosporidiosis, but unfortunately, it has poor water solubility and bioavailability that greatly affect its efficacy. This study aimed to test the efficacy of NTZ when used in combination with cationic and amphoteric surfactants on murine cryptosporidiosis. Fifty-four white albino female mice were separated into nine groups, with each group containing six mice that had compromised immune systems. <b>GI:</b> normal non-infected non-treated (healthy control). <b>GII:</b> infected, non-treated (infected control); <b>GIII-GXI:</b> infected with <i>Cryptosporidium</i> species oocyst and treated with: <b>GIII:</b> NTZ (NTZ), <b>GIV:</b> cationic surfactant [3-(dodecyl(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)amino)-N,N,N-triethyl-2-hydroxypropan-1-aminium chloride (GDCS)]; <b>GV:</b> amphoteric surfactant [sodium 3-(dodecyl(3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)amino)-2-hydroxypropane-1-sulfonate (GDAS)]; <b>GVI</b>: NTZ and GDCS; <b>GVII:</b> NTZ and GDAS; <b>GVIII:</b> NTZ and GDCS in a critical micelle concentration (CMC); <b>GIX:</b> NTZ and GDAS in CMC. Parasitological, and histopathological, examinations were done. Parasitological examination revealed a statistically significant difference (<i>P</i> < 0.001) between the different test and control groups. GIX showed the best results, with the highest percentage of reduction of oocysts in the stool (98.21%) which was statistically significant from other test and control groups. Histopathological examination revealed marked improvement in small intestinal villi, liver, and lung tissues when NTZ was used in combination with GDCS, and GDAS, especially with GDAS CMC. Therefore, surfactant could be an excellent adjuvant therapy when combined with NTZ in the treatment of cryptosporidiosis, especially GDAS CMC.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1068-1085"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-05-27DOI: 10.1007/s12639-025-01818-y
Jonathan Jaime G Guerrero, Vicente Y Belizario
Pulmonary tuberculosis (PTB) remains a major public health concern in several regions of the Philippines and in many parts of Southeast Asia. Overlapping with it in terms of clinical manifestations is pulmonary paragonimiasis or lung fluke disease. Paragonimiasis, a foodborne trematode infection, may be hidden in plain sight in the setting of a high burden of PTB. This raises questions about how much reported data on PTB is paragonimiasis and how much coinfection exists with PTB and this food-borne trematode infection. This research draws lessons from Zamboanga Peninsula in the Philippines, a region with considerable data on both disease entities. In this paper, a review of available data from published literature and from the country's Department of Health registry was undertaken. Results show that TB remains to be a major public health concern in the region. Coincidentally, paragonimiasis also exists in many parts of the region alongside TB, with Paragonimiasis being more common than PTB in some areas. The approach from Zamboanga Peninsula may be used to generate evidence from other regions and become the basis for national policy formulation. The results support an integrated policy for surveillance, and control. Capacity building and active surveillance may be combined to enhance case finding, treatment, and generation of data for mapping and targeted interventions for integrated tuberculosis-paragonimiasis control. These learnings may be applicable to other parts of the Philippines and Southeast Asia where there may be known or likely co-endemicity of the two diseases.
{"title":"Hidden in plain sight: lessons on misdiagnosis of pulmonary paragonimiasis in a setting of high burden of pulmonary tuberculosis from Zamboanga Peninsula, the Philippines.","authors":"Jonathan Jaime G Guerrero, Vicente Y Belizario","doi":"10.1007/s12639-025-01818-y","DOIUrl":"https://doi.org/10.1007/s12639-025-01818-y","url":null,"abstract":"<p><p>Pulmonary tuberculosis (PTB) remains a major public health concern in several regions of the Philippines and in many parts of Southeast Asia. Overlapping with it in terms of clinical manifestations is pulmonary paragonimiasis or lung fluke disease. Paragonimiasis, a foodborne trematode infection, may be hidden in plain sight in the setting of a high burden of PTB. This raises questions about how much reported data on PTB is paragonimiasis and how much coinfection exists with PTB and this food-borne trematode infection. This research draws lessons from Zamboanga Peninsula in the Philippines, a region with considerable data on both disease entities. In this paper, a review of available data from published literature and from the country's Department of Health registry was undertaken. Results show that TB remains to be a major public health concern in the region. Coincidentally, paragonimiasis also exists in many parts of the region alongside TB, with Paragonimiasis being more common than PTB in some areas. The approach from Zamboanga Peninsula may be used to generate evidence from other regions and become the basis for national policy formulation. The results support an integrated policy for surveillance, and control. Capacity building and active surveillance may be combined to enhance case finding, treatment, and generation of data for mapping and targeted interventions for integrated tuberculosis-paragonimiasis control. These learnings may be applicable to other parts of the Philippines and Southeast Asia where there may be known or likely co-endemicity of the two diseases.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"908-916"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-04-19DOI: 10.1007/s12639-025-01793-4
Paul Terkende Hambesha, Ochuko Orakpoghenor, Paul Ayuba Abdu, Isa Danladi Jatau, Tagang Aluwong
The role of complementary and alternative medicines for the treatment of various diseases is gaining serious attention. This study evaluated the haematological changes induced by Eimeria tenella challenge in broiler chickens following pre-administration with methanol extracts of Ganoderma lucidum, Vernonia amygdalina and Vitellaria paradoxa. One hundred one-day-old Abor acre broiler chicks obtained from a commercial hatchery were randomly divided into 10 groups (A1, B1, C1, D1, A2, B2, C2, D2, E, and F) of 10 birds each. From 14 to 20 days of age (doa), A1 and A2 were administered G. lucidum (250 mg/kg); B1 and B2 V. amygdalina (2000 mg/kg); C1 and C2 V. paradoxa (250 mg/kg); D1 and D2 Amprolium (100 g/100 L drinking water); while E, and F were positive, and negative controls, respectively. At 21 doa, A2, B2, C2, D2 and E were challenged with 104E. tenella sporulated oocysts orally. Blood was collected at 14, 21 and 28 doa, and processed for haematology. Results revealed no significant difference (P > 0.05) in the haematological parameters in all groups of broiler chickens at 14 and 21 doa. At 28 doa, packed cell volume (PCV), and haemoglobin (Hb) concentration were significantly (P < 0.05) lower while total red blood cells were non-significantly (P > 0.05) lower in group E than in A2, B2, C2 and D2. Total leukocyte and heterophil counts were significantly (P < 0.05) higher while lymphocyte count and heterophil/lymphocyte ratio were non-significantly (P > 0.05) higher in group E than in A2, B2, C2 and D2. The prophylactic administration of G. lucidum, V. amygdalina leaf and V. paradoxa stem bark methanolic extracts significantly ameliorated the changes in PCV, Hb concentration, total leukocyte and heterophil counts induced by E. tenella challenge in the broiler chickens. Further studies that explore the mechanisms by which these extracts ameliorated the haematological changes via their prophylactic anticoccidial activities should be conducted.
{"title":"Pre-administration with <i>Ganoderma lucidum</i>, <i>Vernonia amygdalina</i> and <i>Vitellaria paradoxa</i> methanolic extracts ameliorated haematological changes induced by <i>Eimeria tenella</i> challenge in broiler chickens.","authors":"Paul Terkende Hambesha, Ochuko Orakpoghenor, Paul Ayuba Abdu, Isa Danladi Jatau, Tagang Aluwong","doi":"10.1007/s12639-025-01793-4","DOIUrl":"https://doi.org/10.1007/s12639-025-01793-4","url":null,"abstract":"<p><p>The role of complementary and alternative medicines for the treatment of various diseases is gaining serious attention. This study evaluated the haematological changes induced by <i>Eimeria tenella</i> challenge in broiler chickens following pre-administration with methanol extracts of <i>Ganoderma lucidum</i>, <i>Vernonia amygdalina</i> and <i>Vitellaria paradoxa</i>. One hundred one-day-old Abor acre broiler chicks obtained from a commercial hatchery were randomly divided into 10 groups (A1, B1, C1, D1, A2, B2, C2, D2, E, and F) of 10 birds each. From 14 to 20 days of age (doa), A1 and A2 were administered <i>G. lucidum</i> (250 mg/kg); B1 and B2 <i>V. amygdalina</i> (2000 mg/kg); C1 and C2 <i>V. paradoxa</i> (250 mg/kg); D1 and D2 Amprolium (100 g/100 L drinking water); while E, and F were positive, and negative controls, respectively. At 21 doa, A2, B2, C2, D2 and E were challenged with 10<sup>4</sup> <i>E</i>. <i>tenella</i> sporulated oocysts orally. Blood was collected at 14, 21 and 28 doa, and processed for haematology. Results revealed no significant difference (<i>P</i> > 0.05) in the haematological parameters in all groups of broiler chickens at 14 and 21 doa. At 28 doa, packed cell volume (PCV), and haemoglobin (Hb) concentration were significantly (<i>P</i> < 0.05) lower while total red blood cells were non-significantly (<i>P</i> > 0.05) lower in group E than in A2, B2, C2 and D2. Total leukocyte and heterophil counts were significantly (<i>P</i> < 0.05) higher while lymphocyte count and heterophil/lymphocyte ratio were non-significantly (<i>P</i> > 0.05) higher in group E than in A2, B2, C2 and D2. The prophylactic administration of <i>G. lucidum</i>, <i>V. amygdalina</i> leaf and <i>V. paradoxa</i> stem bark methanolic extracts significantly ameliorated the changes in PCV, Hb concentration, total leukocyte and heterophil counts induced by <i>E. tenella</i> challenge in the broiler chickens. Further studies that explore the mechanisms by which these extracts ameliorated the haematological changes via their prophylactic anticoccidial activities should be conducted.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"1100-1108"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-07-31DOI: 10.1007/s12639-025-01838-8
Hinpetch Daungsupawong, Viroj Wiwanitkit
This study aimed to assess the effectiveness of ChatGPT, an AI-based language model, in aiding healthcare professionals with selecting suitable medications for the treating of leishmaniasis. A panel of medical experts and specialists in tropical diseases assessed the recommendations provided by ChatGPT for 10 hypothetical clinical scenarios related to leishmaniasis. The main objective was to determine the utility of ChatGPT in facilitating informed decision-making regarding drug choices for managing leishmaniasis. ChatGPT consistently provided valuable suggestions for potential drug repurposing in the treatment of leishmaniasis across all scenarios, aligning with current medical research. Despite the lack of specific treatment guidelines, ChatGPT's suggestions proved beneficial, presenting potential avenues for medication repurposing. These findings suggest that ChatGPT shows promise as a useful tool for drug repurposing in leishmaniasis therapy, assisting in the identification of potential pharmaceutical options. However, it is important to acknowledge certain limitations, such as the requirement for additional clinical data and the inability to adjust therapy.
{"title":"AI-powered medicine repurposed to identify new leishmaniasis treatments.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1007/s12639-025-01838-8","DOIUrl":"https://doi.org/10.1007/s12639-025-01838-8","url":null,"abstract":"<p><p>This study aimed to assess the effectiveness of ChatGPT, an AI-based language model, in aiding healthcare professionals with selecting suitable medications for the treating of leishmaniasis. A panel of medical experts and specialists in tropical diseases assessed the recommendations provided by ChatGPT for 10 hypothetical clinical scenarios related to leishmaniasis. The main objective was to determine the utility of ChatGPT in facilitating informed decision-making regarding drug choices for managing leishmaniasis. ChatGPT consistently provided valuable suggestions for potential drug repurposing in the treatment of leishmaniasis across all scenarios, aligning with current medical research. Despite the lack of specific treatment guidelines, ChatGPT's suggestions proved beneficial, presenting potential avenues for medication repurposing. These findings suggest that ChatGPT shows promise as a useful tool for drug repurposing in leishmaniasis therapy, assisting in the identification of potential pharmaceutical options. However, it is important to acknowledge certain limitations, such as the requirement for additional clinical data and the inability to adjust therapy.</p>","PeriodicalId":16664,"journal":{"name":"Journal of Parasitic Diseases","volume":"49 4","pages":"979-986"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12602786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145504834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}